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085, before vs. after NO inhalation, respectively). Procedure-related complications were observed in 46 sessions (13.6%). The incidence of hemoptysis was significantly higher in the NO group than in the non-NO group (20.8% vs. 10.9%; p = 0.031). In contrast, all fatal complications (death and use of positive pressure ventilation) occurred in the non-NO group, but the difference was not statistically significant (0 sessions [0.0%] vs. selleck chemicals llc 7 sessions [2.6%], p = 0.353). Inhaled NO acts as a selective pulmonary vasodilator in CTEPH/CTEPD patients during the BPA procedure.Preclinical and early clinical studies suggest that angiotensin-converting enzyme type 2 activity may be impaired in patients with pulmonary arterial hypertension (PAH); therefore, administration of exogenous angiotensin-converting enzyme type 2 (ACE2) may be beneficial. This Phase IIa, multi-center, open-label, exploratory, single-dose, dose-escalation study (NCT03177603) assessed the potential vasodilatory effects of single doses of GSK2586881 (a recombinant human ACE2) on acute cardiopulmonary hemodynamics in hemodynamically stable adults with documented PAH who were receiving background PAH therapy. Successive cohorts of participants were administered a single intravenous dose of GSK2586881 of 0.1, 0.2, 0.4, or 0.8 mg/kg. Dose escalation occurred after four or more participants per cohort were dosed and a review of safety, tolerability, pharmacokinetics, and hemodynamic data up to 24 h postdose was undertaken. The primary endpoint was a change in cardiopulmonary hemodynamics (pulmonary vascular resistance, cardiac index, and mean pulmonary artery pressure) from baseline. Secondary/exploratory objectives included safety and tolerability, effect on renin-angiotensin system peptides, and pharmacokinetics. GSK2586881 demonstrated no consistent or sustained effect on acute cardiopulmonary hemodynamics in participants with PAH receiving background PAH therapy (N = 23). All doses of GSK2586881 were well tolerated. GSK2586881 was quantifiable in plasma for up to 4 h poststart of infusion in all participants and caused a consistent and sustained reduction in angiotensin II and a corresponding increase in angiotensin (1-7) and angiotensin (1-5). While there does not appear to be a consistent acute vasodilatory response to single doses of GSK2586881 in participants with PAH, the potential benefits in terms of chronic vascular remodeling remain to be determined.The post 3 kidney transplant course of pretransplant echocardiographically-defined pulmonary hypertension (PH) was reviewed in 115 patients. Of these 61 patients (the largest cohort reported to date), underwent 160 "for indication" echocardiograms posttransplant (mean echocardiograms per patient 2.6 ± 2.3). Patients undergoing posttransplant echocardiograms demonstrated greater risks for worse outcomes than those without posttransplant echocardiograms; however, there was no difference in mortality, death-censored graft failure or the composite of death or graft failure between these two groups. Of patients tested, 36 (59%) showed resolution of PH at a median of 37.5 months. Six patients (16.7%) in whom PH resolved (at a median of 29 months), experienced recurrence of PH after an interval of 48 months. No pretransplant demographic or echocardiographic characteristics distinguished those in whom PH persisted versus resolved. Though there was no difference in the risk for mortality or death-censored graft loss between the two groups at 3 and 5 years, there was a higher risk for the composite of mortality or graft loss at three but not at five years in the group with persistent PH. In conclusion, echocardiographically defined PH resolved in 59% of patients following kidney transplantation; but irrespective of resolution there was no clear association with worse outcome.Periodic repetition of right heart catheterization (RHC) in pulmonary arterial hypertension (PAH) can be challenging. We evaluated the correlation between RHC and cardiopulmonary exercise test (CPET) aiming at CPET use as a potential noninvasive tool for hemodynamic burden evaluation. One hundred and forty-four retrospective PAH patients who had performed CPET and RHC within 2 months were enrolled. The following analyses were performed (a) CPET parameters in hemodynamic variables tertiles; (b) position of hemodynamic parameters in the peak end-tidal carbon dioxide pressure (PETCO2) versus ventilation/carbon dioxide output (VE/VCO2) slope scatterplot, which is a specific hallmark of exercise respiratory abnormalities in PAH; (c) association between CPET and a hemodynamic burden score developed including mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index, and right atrial pressure. VE/VCO2 slope and peak PETCO2 significantly varied in mPAP and PVR tertiles, while peak oxygen uptake (peak VO2) and O2 pulse varied in the tertiles of all hemodynamic parameters. PETCO2 versus VE/VCO2 slope showed a strong hyperbolic relationship (R 2 = 0.7627). Patients with peak PETCO2 > median (26 mmHg) and VE/VCO2 slope  median. Multivariate analysis individuated peak VO2 (p = 0.0158) and peak PETCO2 (p = 0.0089) as hemodynamic score independent predictors; the formula 11.584 - 0.0925 × peak VO2 - 0.0811 × peak PETCO2 best predicts the hemodynamic score value from CPET data. A significant correlation was found between estimated and calculated scores (p  less then  0.0001), with a precise match for patients with mild-to-moderate hemodynamic burden (76% of cases). The results of the present study suggest that CPET could allow to estimate the hemodynamic burden in PAH patients.Plasma volume status (PVS) is a noninvasive estimate of intravascular volume status. We studied the utility of PVS to predict short-term outcomes in patients with pulmonary hypertension. Patients with lower PVS had decreased risk of hospitalization and death within 90 days of clinic visit, compared to those with higher PVS.Pulmonary tumor thrombotic microangiopathy (PTTM) is a rapidly progressive subtype of pulmonary hypertension (PH) associated with impaired right ventricular adaptation and very poor prognosis in cancer, and its rapid progression makes antemortem diagnosis and treatment extremely difficult. We describe the case of a 35-year-old woman who developed severe PH with subsequent circulatory collapse. The patient was clinically diagnosed with PTTM induced by lung adenocarcinoma harboring the c-ros oncogene 1 (ROS1) rearrangement within 1-2 weeks, while hemodynamics were stabilized by rescue venoarterial extracorporeal membrane oxygenation support. Crizotinib, an oral tyrosine kinase inhibitor targeting anaplastic lymphoma kinase, MET, and ROS1 kinase domains dramatically resolved PH, resulting in more than 3 years of survival. Targeted gene-tailored therapy with mechanical support can improve survival in PTTM.Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD). Little is known about the prevalence and clinical profiles of patients with COPD-PH. We report the clinical characteristics, hemodynamic profiles, and prognosis in a large population of patients with COPD referred for right heart catheterization (RHC). We extracted data from all patients referred for RHC between 1997 and 2017 in Vanderbilt's deidentified medical record. PH was defined as mean pulmonary artery pressure >20 mmHg. Pre- and postcapillary PH were defined according to contemporary guidelines. COPD was identified using a validated rules-based algorithm requiring international classification of diseases codes relevant to COPD. We identified 6065 patients referred for RHC, of whom 1509 (24.9%) had COPD and 1213 had COPD and PH. Patients with COPD-PH had a higher prevalence of diabetes, atrial fibrillation, and heart failure compared with COPD without PH. Approximately 55% of patients with COPD-PH had elevated left ventricle (LV) filling pressure. Pulmonary function testing data from individuals with COPD-PH revealed subtype differences, with precapillary COPD-PH having lower diffusion capacity of the lungs for carbon monoxide (DLCO) values than the other COPD-PH subtypes. Patients with COPD-PH had significantly increased mortality compared with COPD alone (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.28-2.26) with the highest mortality among the combined pre- and postcapillary COPD-PH subgroup (HR 2.39; 95% CI 1.64-3.47). PH is common among patients with COPD referred for RHC. The etiology of PH in patients with COPD is often mixed due to multimorbidity and is associated with high mortality, which may have implications for risk factor management.Real-world dosing and titration of parenteral (subcutaneous, SC; intravenous, IV) prostacyclin, a mainstay of pulmonary arterial hypertension (PAH) treatment, is not always consistent with prescribing information or randomized trials and has yet to be adequately characterized. The current study describes real-world outpatient dosing and titration patterns over time, in PAH patients initiated on SC or IV treprostinil. A longitudinal, cross-sectional analysis of medication shipment records from US specialty pharmacy services between 2009 and 2018 was conducted to determine dosing and titration patterns of SC or IV treprostinil in the outpatient setting beginning with the patient's first shipment. The sample for analysis included shipment records for 2647 patients (IV = 1040, SC = 1607). Although more patients were started on SC treprostinil than IV, median initial outpatient IV treprostinil dose (11 ng/kg/min at month on therapy one [MOT1]) was consistently and statistically significantly higher than initial outpatient SC dose (7.5 ng/kg/min at MOT1; p  less then  0.01). However, the SC treprostinil dose acceleration rate (DAR) was more aggressive from MOT1 to MOT6, MOT12, and MOT24, leading to a higher dose achieved at later timepoints. All between-group DAR differences were statistically significant (p  less then  0.001). This study provides evidence that real-world prescribing patterns of parenteral treprostinil in the outpatient setting differs from dosing described in pivotal trials, with important differences between SC and IV administration. Although initial outpatient IV treprostinil dosing was higher, SC titration was accelerated more aggressively and a higher dose was achieved by MOT3 suggesting that factors specific to SC administration (e.g., site pain) may not limit dosing and titration as previously thought.BMP signaling deficiency is evident in the lungs of patients with pulmonary arterial hypertension. We demonstrated that PHD2 deficiency suppresses BMP signaling in the lung endothelial cells, suggesting the novel mechanisms of dysregulated BMP signaling in the development of pulmonary arterial hypertension.Hepatoma-derived growth factor (HDGF) was previously shown to be associated with increased mortality in a small study of idiopathic and connective tissue disease-associated pulmonary arterial hypertension (PAH). In this study, we measured serum HDGF levels in a large multicenter cohort (total 2017 adult PAH-Biobank enrollees), we analyzed the associations between HDGF levels and various clinical measures using linear or logistic regression models. Higher HDGF levels were found to be significantly associated with worse pulmonary hemodynamics, prostacyclin treatment; among PAH subtypes, higher HDGF levels were most associated with portopulmonary hypertension (beta = 0.469, p  less then  0.0001). Both Kaplan-Meier curve and Cox proportional hazard regression demonstrated that higher HDGF levels are associated with a higher risk of mortality (COX hazard ratio 1.31, p  less then  0.0001). Further, in the Sugen hypoxia (SuHx) rat model, the highest HDGF levels were post-pulmonary circulation, and HDGF levels significantly increased with the development of PAH.